血管紧张素转换酶抑制剂和血管紧张素Ⅱ受体拮抗剂抑制胃癌血管生成

Effects of angiotensin converting enzyme inhibitors and angiotensin Ⅱ receptor blockers on angiogenesis of gastric cancer in a nude mouse model

目的建立人胃癌裸鼠移植瘤模型，观察血管紧张素转换酶抑制剂（ACEI）及血管紧张素Ⅱ受体拮抗剂（ARB）对胃癌生长和血管生成的影响。方法设立对照组、ACEI组（又分为培哚普利组和卡托普利组）、ARB组（又分为氯沙坦组和缬沙坦组），定期观察各组肿瘤生长情况并测量肿瘤体积，3周后取出肿瘤标本，采用免疫组化测定各组的基质金属蛋白酶7（MMP-7）、血管内皮生长因子（VEGF）的表达和癌周微血管密度（MVD）。结果ACEI组和ARB组移植瘤体积与对照组相比．均明显受到抑制（P〈0．011。ACEI组和ARB组肿瘤组织中的VEGF和MVD与对照组比较，均显著降低（P〈0．05和P〈0．01）。ACEI组对MMP-7的表达具有抑制作用（P〈0．05）；而ARB对MMP-7无显著抑制作用。结论ACEI和ARB能明显抑制人胃癌裸鼠移植瘤的生长以及新生血管的形成。

Objective To observe the effects of angiotensin converting enzyme inhibitors （ACEI）and angiotensin Ⅱ receptor blocker （ARB） on tumor growth and angiogenesis in implanted gastric cancer mouse model, and to explore the probable mechanism of ACEI and ARB anticancer effect. Methods Nude mouse model with human gastric cancer was established by subcutaneously inoculating human gastric cancer cell line SGC-7901. One week later, 60 mice were randomly divided into 5 groups： control group, perindopril group, captopril group, losartan group, and valsartan group. These groups respectively received the normal saline, perindopril （2 mg/kg）, captopril （5 mg/kg）, losartan （50 mg/kg）,valsartan （40 mg/kg） by gavage once a day. Twenty-one days after treatment the tumors were removed and the tissues were stained by imnmnohistochemistry method to observe the expression of VEGF, MMP-7 and microvessel density （MVD）. Results In all the ACEI and ARB groups, tumor volumes were significantly inhibited and MVD also decreased significantly as compared with control group （all P〈0.01）. In captopril and perindopril groups, the expression of VEGF and MMP-7 decreased significantly as compared with control group （all P〈0.05）. In losartan and valsartan group, the expressions of VEGF were significantly decreased as compared with control group （all P〈 0.05）. The expressions of MMP-7 between ARB groups and control group were not significantly different. Conclusion ACEI and ARB can inhibit the tumor growth in gastric cancer model and suppress the angiogenesis of the tumor.